UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and east Asians: a Mendelian randomization study

Borges, Maria-Carolina; Haycock, Phillip; Zheng, Jie; Hemani, Gibran; Howe, Laurence J; Schmidt, A Floriaan; Staley, James R; ... Lawlor, Deborah A; + view all (2022) The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and east Asians: a Mendelian randomization study. Human Molecular Genetics 10.1093/hmg/ddac153. (In press). Green open access

[thumbnail of Lumbers_The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and east Asians_AAM.pdf]
Preview
Text
Lumbers_The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and east Asians_AAM.pdf

Download (3MB) | Preview

Abstract

Despite early interest, the evidence linking fatty acids to cardiovascular diseases remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the aetiology of several cardiovascular disease endpoints in up to 1 153 768 European (maximum 123 668 cases) and 212 453 East Asian (maximum 29 319 cases) ancestry individuals. As instruments, we selected single nucleotide polymorphisms (SNP) mapping to genes with well-known roles in PUFA (i.e. FADS1/2 and ELOVL2) and MUFA (i.e. SCD) biosynthesis. Our findings suggest that higher PUFA biosynthesis rate (proxied by rs174576 near FADS1/2) is related to higher odds of multiple cardiovascular diseases, particularly ischemic stroke, peripheral artery disease and venous thromboembolism, whereas higher MUFA biosynthesis rate (proxied by rs603424 near SCD) is related to lower odds of coronary artery disease among Europeans. Results were unclear for East Asians as most effect estimates were imprecise. By triangulating multiple approaches (i.e. uni-/multi-variable Mendelian randomization, a phenome-wide scan, genetic colocalization and within-sibling analyses), our results are compatible with higher low-density lipoprotein (LDL)-cholesterol (and possibly glucose) being a downstream effect of higher PUFA biosynthesis rate. Our findings indicate that PUFA and MUFA biosynthesis are involved in the aetiology of cardiovascular diseases and suggest LDL-cholesterol as a potential mediating trait between PUFA biosynthesis and cardiovascular diseases risk.

Type: Article
Title: The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and east Asians: a Mendelian randomization study
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/hmg/ddac153
Publisher version: https://doi.org/10.1093/hmg/ddac153
Language: English
Additional information: © The Author(s) 2022. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Infectious Disease Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
URI: https://discovery.ucl.ac.uk/id/eprint/10151958
Downloads since deposit
23Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item